1. Field of the Invention
The present invention relates to the field of medical technology, delivery of materials in the field of medical technology, and the controlled and directed delivery of materials to regions of tissue in the vicinity of cavities.
2. Background of the Art
After tissue has been removed by surgical techniques of various types, cavities remain in remaining tissue in the region of the surgery. The remaining tissue may be subject to various complications after the surgery has been completed. For example, resection margin cavity recurrence after surgical removal of glioblastoma occurs in more than 80% of patients, despite extensive trials of local and generalized treatment regimens. While it is likely that some tumor cells have migrated through white matter tracts to more distal portions of the brain by the time of initial diagnosis, the persistence of tumor cells within the cavity margin eventually creates a local tumor recurrence and also serves as a continuing source for metastasis. Whereas the surgically resected tumor has essentially all cells malignant, the margins of the tumor may be infiltrated with tumor cells in a ratio of 1:10 or so. Therefore, effective post-surgical treatment of the cavity margin will both reduce the morbidity and cost of treating a local recurrence and remove a prominent source of cells for ongoing metastasis to other parts of the brain. It is not realistic to assure the absence of small numbers of tumor cells in such adjacent tissue through extensive removal of tissue, as this would require excessive normal tissue damage. Especially in regions of the brain, extreme excavation of tissue is not a desirable medical procedure.
One relatively standard treatment at this time is that, after surgery has been performed and some recovery period (days or weeks) has been allowed to transpire, a second surgical procedure is performed wherein the region around the cavity is recatheterized. Active material is then infused and diffused about the cavity (into tissue outside the cavity) to chemically attack (preferentially) remaining tumor cells. This type of procedure has a number of defects and disadvantages. A second surgical procedure, with possibly a second distinct bore-hole is required, and the present methods of active ingredient delivery in this procedure tend to be inefficient and inexact.
Among the methods that have been used to treat this problem include: (i) Radiation therapy followed by systemic chemotherapy. The distribution of chemotherapeutic materials administered systemically is highly dependent on the state of the opening of the blood—brain barrier (BBB) and little significant concentration is expected in uncompromised BBB regions; (ii) Placement of wafers containing chemotherapeutics at margin walls. This has the advantage that it can be done at the time of surgery in the operating theater. Its disadvantage is that the chemotherapy spreads by diffusion: the slow rate of diffusive spread combined with high efflux rates of small molecules means the spread is confined to a millimeters instead of centimeters. Despite the FDA approval of this method, it has only marginally improved the survival rate of patients.
Additional alternative methods include (iii) Multicatheter convection—enhanced delivery (CED) from up to four catheters. This is the method that has been most used in clinical trials with CED, and the usual advantage mentioned is the potentially superior spread of infusate from CED over diffusion of the agent. Its principal disadvantage is that it requires a second invasive operation, more so due to the multiple catheters required. Moreover, it is immediately obvious that coverage of a 2 cm margin (which is a thick shell from discrete point or line sources) will require an unacceptable number of catheters, so that CED may fail to cover such a margin. Indeed this has been pointed out as a potential reason for failure of a trial. (iv) It has been advocated that an inside—out approach may be the best modality. Namely, if the infusion occurs from within the cavity, we have, in principle, the entire inner surface of the margin as a source of infusion which should then fill the shell far more uniformly than any of the approaches above.